In clinical microbiology, which mechanism most commonly explains the emergence of drug resistance in Mycobacterium tuberculosis (tuberculosis)?

Introduction / Context:
Drug resistance in Mycobacterium tuberculosis has major public health implications. Unlike many other bacteria that frequently exchange resistance genes via mobile elements, M. tuberculosis typically acquires resistance through spontaneous chromosomal mutations selected during inadequate therapy.

Given Data / Assumptions:

• Bacterium: Mycobacterium tuberculosis.
• Focus: primary cause of resistance acquisition in clinical settings.
• Horizontal gene transfer is rare in M. tuberculosis populations.

Concept / Approach:
Resistance to isoniazid, rifampicin, fluoroquinolones, and other agents often maps to point mutations in genes such as katG, inhA promoter, rpoB, and gyrA/gyrB. Selection occurs under suboptimal drug exposure, poor adherence, or monotherapy. This is a classical mutation–selection model rather than plasmid-mediated transfer.

Step-by-Step Solution:

Verification / Alternative check:
Global surveillance and molecular diagnostics (e.g., rpoB mutation detection by molecular assays) support mutation-driven resistance, confirming the mechanism.

Why Other Options Are Wrong:

• Transduction/Transformation/Conjugation: Horizontal gene transfer mechanisms are not the predominant pathway in M. tuberculosis; plasmids and phage-mediated exchanges are uncommon in clinical strains.

Common Pitfalls:

• Assuming resistance is always plasmid-borne as in Enterobacterales; M. tuberculosis is different.
• Confusing selection (clinical mismanagement) with mutation origin.

Final Answer:
Mutation